Objectives To examine the effect of topical antiandrogens on the hyperplastic sebaceous glands of male fuzzy rats, a model of human acne. ABSTRACT:Male fuzzy rats exhibit brownish seborrheic skin and hyperplastic sebaceous glands with microcomedo-like ducts. These changes are abolished by castration and reappear after testosterone implant. Using this model for human acne, we examined the effects of two inhibitors of 5 a-reductase, MK386 (MK), type I, and finasteride (FS), type II, (formulated by Merck Res. Lab.), on suppression of sebaceous glands. The enzyme, 5 a-reductase, converts circulating testosterone to dihydrotestosterone which is a potent androgen for postpubertal growth of the prostate, hair follicles, and sebaceous glands. FS and MK inhibit both isozymes of rat 5 a-reductase, but FS is more potent than MK. MK, 0.01, 0.1, and 1%, and FS, 0.025, 0.05, and 0.1% solutions (0.5 ml per rat), were topically applied on the lower backs of 30 day old fuzzy rats, once per day, for 8 weeks. The appearance of seborrhea was recorded by weekly photographs and the size of the glands was analyzed using serial frozen sections of glands attached to split epidermis and stained with osmium. DNA synthesis in sebocytes was examined by in vivo uptake of bromodeoxyuridine (20 mg/100 gm) and its immunocytochemical staining. Four weeks after application, seborrhea was significantly reduced by both 1% MK and 0.1% FS. However, significant shrinkage of glandular lobes was mostly seen in FS-treated rats; a 30% reduction with 0.1% FS and 10% with 0.05% FS. MK induced a slight shrinkage (10% in the 1% group), but it caused marked diminution of the ductal dilatation which is not seen in FS groups. The numbers of DNA synthesis cells in the glands corresponded to the reduction rate of glandular lobes with both MK and FS. FS, but not MK, induced a dose-dependent reduction of prostate weight. Although both inhibitors induce a suppression of androgen-dependent hyperactive sebaceous glands, it appears that FS has a greater ability to counteract the androgenic action of sebocytes than MK. MK tends to suppress the microcomedo of the sebaceous duct in fuzzy rats. Keywords sebaceous gland antiandrogen mutant rat